The objective of this research is to develop an integrated system for high throughout DNA sequencing. This will include the automation of plaque selection, template preparation, sequencing reaction assembly, gel loading, and horizontal ultrathin gel electrophoresis. The system will be designed to be reliable, modular and as completely integrated as possible. This can be accomplished by using standard industrial robotic modules to perform well understood molecular biology techniques. The automated system will be constructed in the first year of the project and then installed at a production sequencing laboratory for extensive testing. Several iterations of testing and redesign in the second year will be required to construct a version that is ready for implementation in a genome sequencing laboratory. The system, when completed, will be able to process 2Mb of raw sequence per day with a technical staff of approximately three people. It is anticipated that these integrated systems will substantially reduce the cost of DNA sequencing and meet the goals of the Human Genome Initiative.